Cholinergics

• Remember, these mimic acetylcholine and should therefore yield parasympathetic effects

• Effects include DUMBELS (defecation, urination, miosis, bronchoconstriction, electrical changes (heart), lacrimation, secretion)

• All activate muscarinic receptors, some also activate nicotinics (carbachol, e.g.)

• Low oral bioavailability

• Contraindicated in Parkinson’s, pregnancy, etc.

• Due to quarternary state, do not cross BBB

  1. Acetylcholine – short ½ life makes it useless

  2. Methacholine – strong effect on heart (use for paroxysmal atrial tachycardia)

  3. Carbachol – use for open-angle glaucoma, least antagonized by atropine

  4. Bethanecol – give PO or SC but not IV (increased adverse effects).

• Cross BBB to cause arousal, excitation, headache, and tremors

• Stimulation of salivation and sweating is particularly prominent

  1. Muscarine – no therapeutic uses, found in poisonous mushrooms (mycetism)

  2. Pilocarpine – use for open-angle glaucoma, xerostomia (Sjörgen’s syndrome)

• Effects are dose dependent

• Hydrolyzed by plasma esterases

  1. Edrophonium – use to diagnose myasthenia gravis; never for cholinergic crisis

  2. Physostigmine – crosses BBB, use to treat antimuscarinic toxicity by atropine, Scopolamine

  3. Neostigmine – does not cross BBB, use to treat myasthenia gravis, can directly activate N_m

  4. Tacrine – used for early Alzheimer’s

• Bind covalently to esteratic site, bond is strengthened by loss of alkyl group (aging)

• Hydrolyzed by paraoxonases

  1. Isofluorophate – Distributed in all tissues, unlike echothiophate

  2. Echothiophate – may be used for open-angle glaucoma if carbachol and pilocarpine prove ineffectual

Category: Pharmacology Notes